Osteoporosis is a major health problem affecting nearly 1.5 million people every year. One-third of all post-menopausal Caucasian women experience at least one osteoporotic fracture during their lifetime. The reduction of sex hormone levels in both men and women increases production of certain factors that lead to osteoporosis. An imbalance between osteoclast and osteoblast activities causes metabolic diseases as osteoporosis (decreased bone mass) and osteopetrosis (increased bone mass). Recently, two soluble and one membrane-bound factors that play important roles in modulating osteoclast differentiation and function were identified. These include Osteoprotegerin ligand (OPGL), RANK (a membrane-bound receptor for OPGL), and Osteoprotegerin (OPG; a soluble receptor for OPGL). Several studies have shown that OPGL acts through RANK to induce osteoclast formation leading to osteoporosis, whereas OPG prevents osteoporosis. Presently, there are no reagent available to measure the levels of these proteins in vivo. In the proposed Phase I study, we will develop monoclonal antibodies for use in a highly sensitive enzyme linked immunoassay to quantitate these factors. We will also select monoclonal antibodies that can neutralize bone resorption activity of osteoclasts. Our Phase II study will test these reagents in animal models. These monoclonal antibodies will be valuable tools for osteoporosis research. PROPOSED COMMERCIAL APPLICATIONS: Osteoporosis is a measure health problem in men and women. A decrease in sex hormone level is one of the cause of osteoporosis. Recently several protein factors have been identified that are important in pathogenesis of disease. Presently no reagents are available, which can measure the levels of these proteins in vivo. Monoclonal antibodies developed during this Phase I study will be valuable tools for measurement of these proteins in biological samples. These antibodies may also have clinical significance in preventing osteoporosis. We expect the market for these reagents to be vast.